Chronic CY 208-243 treatment of MPTP-monkeys causes regional changes of dopamine and GABAA receptors.

Abstract

Four monkeys were rendered parkinsonian by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) i.v. administration and then treated chronically with increasing doses of the D1 agonist CY 208-243 (0.05, 0.1 and 0.5 mg/kg). All animals showed a dose-dependent improvement of their parkinsonian signs after the chronic CY 208-243 treatment; however, half of them developed peak-dose dyskinesias. Dopamine levels were more decreased in the striatum of MPTP-monkeys with dyskinesias compared to those without dyskinesias. [3H]SCH 23390 and [3H]SKF 38393 binding to D1 receptors were in general similar in the striatum of both groups of MPTP-monkeys except [3H]SKF 38393 binding which was lower in the posterior putamen of dyskinetic compared to non-dyskinetic monkeys reflecting decreased coupling of this receptor to G proteins. [3H]spiperone and [3H]N-n-propylnorapomorphine binding to D2 receptors in the striatum tended in general to be higher in dyskinetic compared to non-dyskinetic monkeys, and this reached statistical significance in the posterior caudate labelled with [3H]n-propylnorapomorphine. [3H]muscimol binding to GABAA receptors was significantly higher in the posterior caudate of dyskinetic compared to non-dyskinetic monkeys. The extent of striatal DA denervation, decreased D1, elevated D2 and GABAA receptors, as well as the decrease of the D1/D2 receptor ratio in the posterior striatum may be involved in the appearance of dyskinesias after chronic CY 208-243 treatment.

• Authors: C Gagnon, B Gomez-Mancilla, P J Bédard, T Di Paolo
• Journal: Neuroscience letters (Neurosci Lett) Vol. 163 Issue 1 Pg. 31-5 (Nov 26 1993) ISSN: 0304-3940 [Print] Ireland
• PMID: 7905197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dopamine Agents
• Dopamine D2 Receptor Antagonists
• Indoles
• Phenanthridines
• Receptors, Dopamine D1
• Receptors, Dopamine D2
• Receptors, GABA-A
• CY 208-243
• 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine
• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
• GTP-Binding Proteins
• Dopamine

Topics

• 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (analogs & derivatives, pharmacology)
• Animals
• Autoradiography
• Behavior, Animal (drug effects)
• Brain Chemistry (drug effects)
• Dopamine (metabolism)
• Dopamine Agents (pharmacology)
• Dopamine D2 Receptor Antagonists
• Female
• GTP-Binding Proteins (metabolism)
• Indoles (pharmacology)
• Macaca fascicularis
• Neostriatum (drug effects, metabolism)
• Ovariectomy
• Parkinson Disease, Secondary (chemically induced, metabolism)
• Phenanthridines (pharmacology)
• Receptors, Dopamine D1 (antagonists & inhibitors, drug effects)
• Receptors, Dopamine D2 (drug effects)
• Receptors, GABA-A (drug effects)